Mannheimia haemolytica (M. haemolytica) is the most significant bacterial pathogen of respiratory disease in cattle, sheep, goats and other ruminants, and causes extensive economic losses world-wide8. M. haemolytica is commonly found in the nasopharynx of healthy ruminants. In conjunction with active viral infection and stress factors, M. haemolytica migrates to the lungs, where it multiplies rapidly, and causes a fibrinonecrotic pleuropneumonia. M. haemolytica produces several virulence factors8. Based on the observation that leukotoxin-deletion mutants (Lkt-deletion mutants) of M. haemolytica cause reduced mortality and much milder lung lesions than the wild-type organisms, Lkt is considered as the most important virulence factor of this organism9-13. Lkt belongs to the family of RTX (repeats in toxins) toxins, and shares extensive homology with the exotoxins produced by other gram-negative bacteria such as Escherichia coli14, Actinobacillus pleuropneumoniae15, and Actinobacillus actinomycetemcomitans16. Cytolytic activity of M. haemolytica Lkt is specific for ruminant leukocytes17-18. Although all the subsets of leukocytes are susceptible to the cytolytic effects of Lkt, PMNs are the most susceptible subset19. PMN-depletion mitigates the lung injury in calves caused by M. haemolytica infection20. Therefore, Lkt-induced PMN lysis and degranulation are the primary causes of acute inflammation and lung injury characteristic of pneumonic pasteurellosis8,13,20.
There is, therefore a pronounced need in the art for novel and efficacious compositions and methods for treating or preventing conditions and/or diseases associated with M. haemolytica (e.g., in mammals, ruminants).